CRTH2 is a G-protein-coupled chemoattractant receptor, expressed on Th2 cells and eosinophilic granulocytes. Th2-polarization has been observed inallergic diseases, such as asthma, allergic rhinitis, atopic dermatitis and allergic conjunctivitis. Th2 cells generate Th2 cells factors, such as IL-4, IL-5 and IL-3, to regulate allergic diseases. In allergic diseases, these Th2 cells factors directly or indirectly induce immigration, activation, priming and prolonged survival of effector cells, such as eosinophilic granulocytes and basophilic granulocytes.
PGD2 (prostaglandin D2), a ligand for CRTH2, is produced from mast cells and other important effector cells in allergic diseases. In human cells, PGD2 induces immigration and activation of Th2 cells, eosinophilic granulocytes and basophilic via CRTH2. Therefore, antagonists inhibiting the combination of CRTH2 and PGD2 should be useful for the treatment of allergic diseases, such as asthma, allergic rhinitis, atopic dermatitis, and allergic conjunctivitis.
In addition, several series of experiments evidences have demonstrated the role of eosinophilic granulocytes in nasal sinusitis and Churg-Strauss syndrome. In the tissues of these patients, mast cells can be observed to be colocalized with eosinophilic granulocytes. It is suggested that PGD2 production from mast cells induces the recruitment of eosinophilic granulocytes. Therefore, antagonists of CRTH2 receptors are also useful for the treatment of other eosinophilic granulocytes-related diseases such as Churg-Strauss syndrome and nasal sinusitis. CRTH2 antagonists can also be useful for the treatment of some basophilic granulocytes-related diseases such as basophilic leukemia, chronic urticaria and basophilic leukocytosis, because of high expression of CRTH2 on basophilic granulocytes.
Ramatroban is commercially available as an antagonist of thromboxane A2 receptor, having an extremely high effect of activating platelet, and a weak antagonism toward CRTH2 receptors. The selectivity thereof is low, and the main adverse reactions are suggillation, prolonged prothrombin time/activated partial thromboplastin time, and subcutaneous hemorrhage.

Currently, there is no medicamentation with an effective antagonism toward CRTH2 in the market. Therefore, there is a need to develop compounds with high selecrivity, high activity, and novel structure, to optimize physical-chemical property and increase druggability.